The aim of the proposed project is to investigate the possible neurochemical mechanisms underlying morphine dependence and tolerance. Evidence from several studies suggests that the changes in dopamine receptor sensitivity, which occurs during chronic morphine treatment, are important aspects of opiate tolerance and dependence. However, the role which these changes have in these phenomena is unclear. Preliminary data indicate that cyclo(Leu-Gly) administered in a manner which blocks the development of physical dependence on and tolerance to morphine also prevents the morphine-induced increase in dopamine receptor sensitivity. In addition, peptide administration after the development of physical dependence and tolerance had already occurred did not alter the display of; physical dependence, tolerance or dopamine receptor supersensitivity. This project is designed to confirm these results as well as to determine the effect of cyclo(Leu-Gly) on dopamine receptor supersensitivity which develops during chronic haloperidol treatment. We also plan to assess the ability of the peptide to alter morphine induced changes in cholinergic systems.